Individual's decisions, from what product to buy to whether to engage in risky behavior, often depend on the choices, behaviors, or states of other people. People, however, rarely have global ...knowledge of the states of others, but must estimate them from the local observations of their social contacts. Network structure can significantly distort individual's local observations. Under some conditions, a state that is globally rare in a network may be dramatically over-represented in the local neighborhoods of many individuals. This effect, which we call the "majority illusion," leads individuals to systematically overestimate the prevalence of that state, which may accelerate the spread of social contagions. We develop a statistical model that quantifies this effect and validate it with measurements in synthetic and real-world networks. We show that the illusion is exacerbated in networks with a heterogeneous degree distribution and disassortative structure.
Epstein-Barr virus (EBV)-associated epithelial cancers, including nasopharyngeal carcinoma (NPC) and approximately 10% of gastric cancers, termed EBVaGC, represent 80% of all EBV-related ...malignancies. However, the exact role of EBV in epithelial cancers remains elusive. Here, we report that EBV functions in vasculogenic mimicry (VM). Epithelial cancer cells infected with EBV develop tumor vascular networks that correlate with tumor growth, which is different from endothelial-derived angiogenic vessels and is VEGF-independent. Mechanistically, activation of the PI3K/AKT/mTOR/HIF-1α signaling cascade, which is partly mediated by LMP2A, is responsible for EBV-induced VM formation. Both xenografts and clinical samples of NPC and EBVaGC exhibit VM histologically, which are correlated with AKT and HIF-1α activation. Furthermore, although anti-VEGF monotherapy shows limited effects, potent synergistic antitumor activities are achieved by combination therapy with VEGF and HIF-1α-targeted agents. Our findings suggest that EBV creates plasticity in epithelial cells to express endothelial phenotype and provides a novel EBV-targeted antitumor strategy.
Abstract
Glucose transporter GLUT1 is a transmembrane protein responsible for the uptake of glucose into the cells of many tissues through facilitative diffusion. Plasma membrane (PM) localization is ...essential for glucose uptake by GLUT1. However, the mechanism underlying GLUT1 PM localization remains enigmatic. We find that GLUT1 is palmitoylated at Cys207, and S-palmitoylation is required for maintaining GLUT1 PM localization. Furthermore, we identify DHHC9 as the palmitoyl transferase responsible for this critical posttranslational modification. Knockout of DHHC9 or mutation of GLUT1 Cys207 to serine abrogates palmitoylation and PM distribution of GLUT1, and impairs glycolysis, cell proliferation, and glioblastoma (GBM) tumorigenesis. In addition, DHHC9 expression positively correlates with GLUT1 PM localization in GBM specimens and indicates a poor prognosis in GBM patients. These findings underscore that DHHC9-mediated GLUT1 S-palmitoylation is critical for glucose supply during GBM tumorigenesis.
Summary
In recent years, consumers have been demanding convenient and healthy foods which have ‘fresh‐like’ characteristics while still being safe and a long shelf‐life. These requirements are hard ...to achieve using existing traditional thermal food processing technologies and the innovative new food process and preservation technologies based on thermal processing systems are needed. However, non‐thermal technologies in food processing do not generate high temperature and use short treatment times. This means that the nutritional components of foodstuffs are better retained, and the sensory properties of foods are less changed compared with traditional thermal processing. The aim of this review was to present non‐thermal technologies applications and its mechanism in food industry in recently, and to explore the potential application prospects of combining non‐thermal treatments applied in food industry because it not only could overcomes the drawback of single technology, but also can enhances the processing efficiency at lower treatment intensity.
The main nonthermal technologies were used in the food processing, and the combining non‐thermal technologies will become the research direction.
Pacemaker cardiomyocytes that create the sinoatrial node are essential for the initiation and maintenance of proper heart rhythm. However, illuminating developmental cues that direct their ...differentiation has remained particularly challenging due to the unclear cellular origins of these specialized cardiomyocytes. By discovering the origins of pacemaker cardiomyocytes, we reveal an evolutionarily conserved Wnt signaling mechanism that coordinates gene regulatory changes directing mesoderm cell fate decisions, which lead to the differentiation of pacemaker cardiomyocytes. We show that in zebrafish, pacemaker cardiomyocytes derive from a subset of Nkx2.5+ mesoderm that responds to canonical Wnt5b signaling to initiate the cardiac pacemaker program, including activation of pacemaker cell differentiation transcription factors Isl1 and Tbx18 and silencing of Nkx2.5. Moreover, applying these developmental findings to human pluripotent stem cells (hPSCs) notably results in the creation of hPSC-pacemaker cardiomyocytes, which successfully pace three-dimensional bioprinted hPSC-cardiomyocytes, thus providing potential strategies for biological cardiac pacemaker therapy.
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•Pacemaker cardiomyocytes derive from a subset of Nkx2.5+ mesoderm•Canonical Wnt5b signaling directs pacemaker cardiomyocyte differentiation in vivo•Wnt5b signaling promotes hPSC-pacemaker cardiomyocyte differentiation in vitro•hPSC-pacemaker cardiomyocytes can pace 3D bioprinted hPSC-cardiomyocytes
Pacemaker cardiomyocytes are crucial for maintaining heart rate. Ren et al. show that these specialized cardiomyocytes originate from outlying Nkx2.5+ mesoderm that responds to canonical Wnt5b signaling in zebrafish. Applying these findings to human pluripotent stem cells (hPSCs) results in the generation of hPSC-pacemaker cardiomyocytes that can pace bioprinted hPSC-cardiomyocytes.
It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential ...route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.
Osteosarcoma, an aggressive malignant cancer, has a high lung metastasis rate and lacks therapeutic target. Here, we reported that chromobox homolog 4 (CBX4) was overexpressed in osteosarcoma cell ...lines and tissues. CBX4 promoted metastasis by transcriptionally up-regulating Runx2 via the recruitment of GCN5 to the Runx2 promoter. The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. Consistently, CK1α suppressed cell migration and invasion through inhibition of CBX4. There was a reverse correlation between CK1α and CBX4 in osteosarcoma tissues, and CK1α was a valuable marker to predict clinical outcomes in osteosarcoma patients with metastasis. Pyrvinium pamoate (PP) as a selective activator of CK1α could inhibit osteosarcoma metastasis via the CK1α/CBX4 axis. Our findings indicate that targeting the CK1α/CBX4 axis may benefit osteosarcoma patients with metastasis.
Biofilms are multicellular communities of microorganisms held together by a self-produced extracellular matrix, which contribute to hygiene problems in the food and medical fields. Both spoilage and ...pathogenic bacteria that grow in the complex structure of biofilm are more resistant to harsh environmental conditions and conventional antimicrobial agents. Therefore, it is important to develop eco-friendly preventive methodologies to eliminate biofilms from foods and food contact equipment. The present paper gives an overview of the current physical methods for biofilm control and removal. Current physical strategies adopted for the anti-biofilm treatment mainly focused on use of ultrasound power, electric or magnetic field, plasma, and irradiation. Furthermore, the mechanisms of anti-biofilm action and application of different physical methods are discussed. Physical strategies make it possible to combat biofilm without the use of biocidal agents. The remarkable microbiocidal properties of physical strategies are promising tools for antimicrobial applications.
The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC ...tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8
T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8
T and immune-suppressive TNFRSF4
Treg cells in tumours might derive from peripheral CX3CR1
CD8
T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3
DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3
DCs, Treg, exhausted CD8
T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.
•Sonication treatment improves the bioactive compounds of grapefruit juice.•Sonication treatment could enhance vitamin C content of grapefruit juice.•Sonication treatment did not affect pH, acidity ...and °Brix of grapefruit juice.•Sonication treatment could enhance cloud value of grapefruit juice.
Sonication is recognised as a potential technique for improvement in the quality of fruit juices. This study was initiated with the objective of evaluating the effect of sonication treatments on some important quality parameters of grapefruit juice such as physico-chemical (pH, acidity and °Brix), Hunter colour values (L∗, a∗ and b∗), cloud value, electrical conductivity, total antioxidant capacity, DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity, ascorbic acid, total phenolics, flavonoids and flavonols. Sonication of grapefruit juice was done in a bath type sonicator at a frequency of 28kHz by maintaining a constant temperature of 20°C. Results showed that there was significant improvement in the cloud value, total antioxidant capacity, DPPH free radical scavenging activity, ascorbic acid, total phenolics, flavonoids and flavonols in all the juice samples sonicated for 30, 60 and 90min but no changes occurred in the pH, acidity and °Brix value as compared to control. Some differences in all the colour values were also observed but overall quality of grapefruit juice was improved, suggesting that sonication technique may successfully be implemented an industrial scale for the processing of grapefruit juice.
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